Pharmacological properties are often dependent on a particular stereochemistry and thus the resolution of a racemic mixture of carboxylic acids containing an alpha chiral carbon is a useful chemical process.
Ruechardt (U.S. Pat. No. 4,691,020) discloses the addition of an optically active alcohol to a ketene, derived from the carboxylic acid analog of the ketene, in the presence of a tertiary amine to yield the respective diastereomeric esters which are converted to the optically active carboxylic acids. Ruechardt describes a preference for 1-aryl C.sub.1-4 alkan-1-ols, although terpene alcohols such as menthol and certain amino alcohols are also mentioned as suitable. The Ruechardt process employs a trialkylamine generally in a concentration of 0.5 to 1 mole of amine per mole of ketene. However, amounts as low as 0.1 mole amine are said to be sufficient. Ruechardt reports optical yields of not less than 30% and in most cases 70 to 80%.
It is highly preferable in commercial resolution processes to employ a readily available and inexpensive alcohol and obtain optical purities of at least 90%; in this regard the preferred alcohols of Ruechardt may not be as widely available and inexpensive as one might prefer. It is an object of the present invention to prepare optically active carboxylic acids in a more economical and simpler manner and in a higher optical purity than hitherto.